As part of a standardized sequence in the NIMH intramural clinical research program at the Neuroscience Center at Saint Elizabeths, patients with schizophrenia are withdrawn from neuroleptic medication and, after clinical relapse, treated with a fixed dose of haloperidol. This in turn allows a variety of studies regarding the pharmacokinetics of haloperidol and the effects of haloperidol and other neuroleptics on central nervous system catecholamines. In addition, the response of these patients to alternative, non-neuroleptic antipsychotic agents is studied. Other pharmacological phenomena being examined in these patients include drug-drug interactions involving haloperidol and several other drugs, especially nicotine and caffeine. The direct effects of haloperidol, nicotine, and caffeine on central catecholaminergic neurotransmitter/receptor function, cellular second messengers, and behavior are also being studied in both clinical and basic science investigations. A final focus is on elucidating the mechanisms involved in the syndrome of polydipsia-hyponatremia, a potentially lethal problem that is relatively common in neuroleptic-treated patients.